Incidence of Mismatch Repair Deficiency in Rectal Cancer and Response to Neoadjuvant Treatment.

INTRODUCTION

The role of mismatch repair deficiency (dMMR) in colon cancer has gained increasing attention due to its association with response to neoadjuvant therapy. In contrast, its significance in rectal cancer remains less comprehensively explored. The influence of dMMR on pathological response following neoadjuvant (chemo)radiotherapy ((C)RT) in rectal cancer is not well understood. This study aimed to compare pathological response to neoadjuvant treatment between dMMR and proficient mismatch repair (pMMR) rectal cancer.

METHODS

A retrospective cohort study was conducted using data from the Dutch ColoRectal Cancer Audit database, including patients who underwent rectal cancer resection between 2018 and 2021. Primary outcomes of this study were the incidence of dMMR and pathological complete response (pCR). A multinomial logistic regression analysis was performed to determine if MMR-status was an independent predictor of pCR.

RESULTS

Out of 8570 patients, MMR-status was determined in 4659 (54.4%) patients, of whom 4516 (96.9%) were pMMR and 143 (3.1%) dMMR. A total of 1562 patients with known MMR-status underwent neoadjuvant treatment. 1514 (96.9%) had pMMR tumors and 48 (3.1%) dMMR tumors. The pCR rate was significantly higher in dMMR patients (29.2%) compared to pMMR patients (13.5%, P = .008). Multivariable logistic regression analysis showed that MMR-status was independently associated with pCR (OR 2.422 [95% CI, 1.236-4.746], P = .010).

CONCLUSION

In this cross-sectional national rectal cancer cohort, the incidence of dMMR was 3.1%, and dMMR appeared to be an independent predictor for higher chance of pathological complete response after neoadjuvant (chemo)radiotherapy.